A series of (arylpiperazinylbutyl)oxindoles as highly potent 5-HT(7) receptor antagonists
has been studied for their selectivity toward the 5-HT(1A) receptor and alpha(1)-adrenoceptor.
Several derivatives exhibited high 5-HT(7)/5-HT(1A) selectivity, and the key structural
factors for reducing undesired alpha(1)-adrenergic receptor binding have also been
identified. Rapid metabolism, a common problem within this family of compounds, could
be circumvented with appropriate substitution patterns on the oxindole carbocycle.
Contrary to expectations, none of the compounds produced an antidepressant-like action
in the forced swimming test in mice despite sufficiently high brain concentrations.
On the other hand, certain analogues showed significant anxiolytic activity in two
different animal models: the Vogel conflict drinking test in rats and the light-dark
test in mice.
